The Division of Neuropathology has served as an informal brain bank from 1981 to 1988. During that period over 200 brains of subjects with cognitive impairment were collected, diagnosed and stored frozen. In the five years of tenure of this grant, 1988-1992, the Neuropathology Core has performed autopsies, examined brains, distributed and stored tissue from cases of dementia and age-matched controls on a regular basis. Two hundred seven brains from cases with dementia and nine control cases have been processed according to this protocol during this five year period, bringing the total number of brains examined and stored to 426. Cerebro-spinal fluid from 65 cases of dementia and 39 controls have also been obtained and stored. In this application we propose to continue to perform the following tasks: 1. Obtain brains at autopsy from approximately 60 subjects with dementia (including subjects from the ADRC patient registry) and 10 age matched control subjects per year. Tissue obtained from these cases will be distributed to various laboratories to be used for the biochemical, morphometric and clinico-pathological studies proposed in this research application and for other ongoing research projects. 2. Provide an accurate neuropathological diagnosis in all the cases examined. 3. Establish density and distribution of neurofibrillary tangles, senile plaques (plaque burden) and neuropil threads in cerebral cortex, as well as a number of neurons and Lewy bodies in substantia nigra and locus coeruleus in cases from the ADRC patient registry. 4. Examine registry cases according to CERAD protocol and transfer them to CERAD. 5. Store fixed and frozen tissues for future studies. The Neuropathology Core not only will provide an essential service to this ADRC but it will also continue to expand and store an invaluable collection of tissue samples from AD and other diseases. This tissue is essential for ongoing research projects supported by other grants at our institution and it will be made available to other institutions in the USA and elsewhere.